The hypothesis underlying the work proposed in this application is that a further understanding of MIS downstream signalling will be useful in elucidating the role of this molecule during development, and potentially in new therapeutics for the treatment of tumors that express the MIS receptor. The applicants propose that: "MIS will bind its type II receptor to activate its type I receptor, which in turn will activate a downstream signal cascade, leading to growth arrest and/or death." The applicants will focus in this project on the MIS specific type 1 receptor. The specific objectives of this application are to: 1) identify the MIS specific type 1 receptor; 2) analyze the role of the MIS type 1 receptor in vivo, using viral vectors, transgenic mice and/or conditional knockout mice; 3) characterize MIS downstream signalling; and 4) identify the target genes regulated by MIS.